医学精品课件：英文班内科学心力衰竭2(PPT 128页)

1、Heart Failure (HF) 第1页，共128页。Heart failure (HF) Conception : heart failure is a final common pathway for many cardiac disorders of diverse etiology and pathogenic mechanisms. It is a clinical syndrome, manifested as a result of the inability of the heart to match its output to the metabolic needs of

2、 the body even though the filling pressure of the heart is adequate.第2页，共128页。Categories of HF1. left, right and whole 2. acute and chronic3. systolic and diastolic 第3页，共128页。stage of HFPre-heart failurePre-clincal heart failureClinical heart failureRefractory end-stage heart failure第4页，共128页。New Yo

3、rk Heart Association Functional ClassificationClass No limitation of physical activity No sympotoms with ordinary exertion Class Slight limitation of physical activity Ordinary activity causes symptoms Class Marked limitation of physical activity Less than ordinary activity causes symptoms Asymptoma

4、tic at rest Class Inability to carry out any physical activity without discomfort Sympotoms at rest第5页，共128页。Stage and Class of HF心衰分期是NYHA分级的补充，但不能替代 NYHA分级NYHA分级 在具体病人可上下变动 (对治疗的反应和/或疾病进程不同)分期 随心脏重构加重只能进展 第6页，共128页。6-min walk distance mild degree： 450mmoderate degree： 150-450msevere degree： 150mEv

5、aluation of chronic HF cardiac function 第7页，共128页。Fundamental causesprimary myocardial diseaseincreased burdens to the heart第8页，共128页。Fundamental causes1. primary decreased myocardial contractility coronary heart disease myocarditis ,cardiomyopathymyocardial metabolic disorder 第9页，共128页。Fundamental

6、causes2. increased burdens to the heart increased afterload (pressure load): hypertension aortic stenosis pulmonary stenosis pulmonary hypertension第10页，共128页。Fundamental causes 2.increased burdens to the heart increased preload (volume load): mitral incompetence aortic incompetence tricuspid incompe

7、tence atrial septal defect (ASD) ventricular septal defect (VSD) patent ductus arteriosus(PDA) hyperthyroidism anemia 第11页，共128页。第12页，共128页。Precipitating causesinfection ,especially respiratory infectionarrhythmias,AFphysical or emotional excesses e.g. pregnancy and deliveryrapid intravenous infusio

8、n , excessive salt taking malpraticeprimary disease deterioration or a new disease happens第13页，共128页。Pathogenesis and pathophysiology1.Compensate heart failure 2. Ventricular remodeling 3.About diastolic insufficiency4. Humoral factors change第14页，共128页。1.Compensate heart failureFrank-Starling princi

9、pleneurohumoral activationmyocardial hypertrophy第15页，共128页。1.Compensate heart failurecardiac dilatation, by way of the Frank-Starling principle ,contractile force increases.第16页，共128页。1 正常静息2 正常活动3 心衰活动3 心衰静息心肌收缩性BADC左室舒张末容量图321 正常和心力衰竭时对机体活动时的代偿情况最大活动活动静息左室作功呼吸困难肺水肿E4 静息 致死性心肌受损第17页，共128页。1.Compens

10、ate heart failureneurohumoral activation a. Increase in sympathetic nervous activity b. RAAS activated (rennin angiotension aldosterone system)第18页，共128页。40年代心衰的概念 心衰 液体潴留向 动脉泵血障碍 静脉回流障碍 肾血流 静脉压 肾静脉 肾微循环 回流障碍 障碍水钠排泄障碍 水钠排泄障碍 水肿 前向衰竭假说 反向衰竭假说 第19页，共128页。60年代心衰的概念 心衰 泵功能障碍 长期静脉和动脉收缩 周围至中央循环 心输出量 前后负荷

11、重新分布 肺血管压力 骨骼肌灌注 左室肥厚/扩张 肺充血 运动能力第20页，共128页。近代心衰的概念 心衰 神经激素异常 长期神经激素激活 细胞因子 水钠潴留 冠脉及全身血管收缩 血管紧张素 过度氧化 和儿茶酚胺 心肌耗氧量 毒性作用 水肿 肺充血 心肌细胞功能障碍 及坏死血流动力学异常 心脏重塑和功能 恶化进展 细胞凋亡 疾病进展 生存率降低第21页，共128页。心力衰竭神经体液的代偿和失代偿交感神经激活水、钠潴留水肿 肺瘀血血流动力学异常血管收缩心肌耗氧量增加心肌氧供应降低心肌细胞功能障碍和坏死心肌重塑功能恶化疾病进展血管紧张素儿茶酚胺毒性作用心肌细胞凋亡肾素-血管紧张素系统激活代偿失代

12、偿心衰症状体征加重治疗目标增强心肌收缩第22页，共128页。心肌细胞死亡心力衰竭心肌细胞死亡+心肌能量消耗后负荷血管收缩心排血量神经体液兴奋RASSASInSP3循环心肌能量消耗胞浆Ca2+cAMP InSP3 心脏心肌松弛性变力效应+心律失常猝死图322 肾素血管紧张素和交感肾上腺素能系统激活时对心脏代偿功能的影响 2. RAAS in Heart Failure第23页，共128页。心衰时的系统 血管紧张素原非肾素 缓激肽径路 血管紧张素（激肽酶）血管紧张素失活片断醛固酮受体 螺内酯 Na+潴留 血管收缩 血管扩张 心肌纤维化 血管肥大 生长抑制 血管损伤 心肌肥大、纤维化 抗增生 血管功

13、能失调 血管保护 交感神经激活 肾保护第24页，共128页。 2. RAAS in Heart Failure第25页，共128页。1.Compensate heart failure myocardial hypertrophy Myocardial cell hypertrophy systole power Not increased number Myocardial fibre increased number energy Myocardial compliance(顺应性）第26页，共128页。2.Ventricular remodeling 第27页，共128页。2.Ventr

14、icular remodeling heart failure is the result of ventricular remodeling.Reduce the myocardial cells decreaseofthesystolicfunction Increased myocardial fibrosis decreaseofthe Ventricular compliance Heart cavity expansionmyocardial hypertrophyextracellular matrixcollagen fibersMyocardial cells Compens

15、ated stage Decompensated stage第28页，共128页。3.about diastolic insufficiency Characteristic : in these cases ,filling of the left or right ventricle is abnormal. Mechanism:myocardial relaxation is impaired.Myocardial compliance decreasing. outcome :diastolic pressures -venouse return-fluid retention , d

16、yspnea , intolerance第29页，共128页。4.some cytofactors take part in heart failure ANP (atrial natriuretic peptide) BNP (brain natriuretic peptide) AVP (arginine vassopressin) Endothelin (NE, angiotensin)Urine volumeperipheral vascularsympathetic nervousRAASVentricular remodeling 第30页，共128页。 Ventricular r

17、emodelingneurohumoral activationheart failure第31页，共128页。Chronic heart failure,CHF第32页，共128页。Clinical manifestations1.Left heart failure pulmonary congestion less cardiac output 2.Right heart failure systemic venous congestion 3.Whole heart failure第33页，共128页。1.Left heart failure 1)dyspnea1.exertional

18、 dyspnea2.paroxysmal nocturnal dyspnea3.orthopnea,4.acute pulmonary edema 第34页，共128页。1.Left heart failure 2)cough, hemoptysis, spit pink sputum 3)fatigue,dizziness,palpitation. 4)oliguria,renal dysfunction 第35页，共128页。sign 1) pulmonary basal rales bilaterally or right-side2) enlarged left heart pulsu

19、s alternans, protodiastolic gallop P2 increasedPulmonary edema第36页，共128页。 2.Right heart failuresymptomabdominal discomfortanorexia(厌食)nausea,vomitexertional dyspnea第37页，共128页。 2.Right heart failuresignliver enlargedascitesdistention of jugular veinshepatojugular reflux(+)peripheral edema , most mark

20、 in dependent partscyanosisprotodiastolic gallop, functional murmurs of tricuspid and pulmonary valve第38页，共128页。3.Whole heart failureLHFRHF第39页，共128页。laboratory examination BNP and NT-proBNP心室扩张心衰张力增大BNP释放第40页，共128页。呼吸困难, 虚弱, 运动受限等症状(NT-proBNP) 慢性心衰 转至心脏专科继续下一步诊断阳性阴性NT-proBNP 临床应用流程图辅助诊断心衰辅助判断进展期心衰患

21、者预后第41页，共128页。laboratory examination CnTIblood routine examination routine urine examinationbiochemical examinationFT3,FT4,TSH第42页，共128页。ECG(electrocardiogram)ischemiaOMIconduction blockarrhysmia第43页，共128页。X-rayPulmonary congestion Pleural effusion Kerlry BRight pulmonary artery broadeningPulmonary

22、hilar butterfly shape第44页，共128页。 EchocardiogramLVEF 50%E/A 1.2LVEDV / LVESVLVEDD / LVESDventricular wall motionCardiac magnetic resonance,CMR99MTC-MIBI SPECT (radionuclide)Coronary angiography第45页，共128页。Cardiac CatheterizationSwan-Ganz PCWP12mmHg CI2.5L/（min.m2）第46页，共128页。Cardiopulmonary Exercise Te

23、sting (CPET)Chronic stable HFMeasurement of rate of oxygen uptake (VO2), rate of CO2 production (VCO2), during maximal “symptom-limited” exercise第47页，共128页。第48页，共128页。Diagnosis and differential diagnosisDiagnosis: medical history + symptoms + signs + examExam:ECG: rarely normal in systolic HF.x-ray:

24、 to detect cardiomegaly and pulmonary congestion.(3) Echocardiogram: It is critical importance . to determine the underlying causes of HF to assess the severity of ventricular dysfunction a. function of contraction: LVEF50% b. function of relaxation: E / A1.2 第49页，共128页。2. Differential diagnosis:car

25、diac asthma Bronchial asthma HistoryHeart diseaseallergichistoryageolderyoungtimenightspringHF signyesnoLung signpulmonary basal rales typical wheezing x-rayPulmonary congestion LV largeEmphysema(肺气肿）alleviate symptoms of dyspnea Diuretics（利尿剂）Digitalis（洋地黄）isosorbide dinitrateafter cough out sputum

26、 Antispasmodic(解痉）第50页，共128页。2. Differential diagnosis: Pericardial effusion, Constrictive pericarditis: distention of jugular veins, hepatojugular reflux(+)liver enlarged, ascitesperipheral edema , most mark in dependent parts medical history signs of heart and perivascular echocardiogram, CMR the

27、most sensitive specific noninvasive method第51页，共128页。2. Differential diagnosis: Hepatocirrhosis with ascites and edema of lower extremity distention of jugular veins (-) hepatojugular reflux(-)第52页，共128页。患者男性，23岁。半年前于“感冒”后出现逐渐加重的胸闷、心悸、气急，近一月经 常出现夜间阵发性呼吸困难，昨晚大便后 又出现呼吸困难并加重，不能平卧， 咳 嗽， 咳泡沫样痰及粉 红色血色痰而就诊

28、入院。病例分析第53页，共128页。病例分析T37.50C、P130次/分、BP120/70mmHg，R30次/分, 明显发绀，大汗，端坐呼吸。颈静脉怒张，心界扩大，第一心音减低和心动过速；心尖区可闻及级收缩期杂音及舒张期奔马律；双肺布满中小水泡音及哮鸣音；肝肿大、肝颈静脉返流征阳性；双下肢轻度水肿。实验室检查：血、尿、粪常规均正常； 肝、肾功能正常第54页，共128页。心电图提示有窦性心动过速伴不同程度的ST-T缺血性改变，同时伴有频发室性早搏； X胸片呈普大型心脏，心胸比率0.66；心脏多普勒检查示心腔均扩大，其中左室扩大最明显，心脏搏动明显减弱；EF（心脏输出量）在29%病例分析第55页

29、，共128页。病例分析诊断：扩张型心肌病 全心衰竭 急性左心衰发作第56页，共128页。诊 断 依据 有扩张性心脏病基础 有全心衰竭表现有引起急性发作的诱因 有急性左心衰的临床表现第57页，共128页。女性患者，36岁。病例主诉：因发热、呼吸急促及心悸3周入院。现病史：4年前病人开始于劳动时自觉心慌气短，近半年来症状加重，同时下肢出现浮肿。1个月前，经常被迫采取端坐位并时常于晚间睡眠时惊醒，气喘不止，经急诊抢救好转。近三周来，出现恶寒发热，咳嗽，痰中时有血丝，心悸气短加重。第58页，共128页。既往史：患者于儿童时期曾因患咽喉肿痛而做扁桃体摘除术，以后时有膝关节肿痛史。病例第59页，共128页

30、。体检：T39.6，P161次/分，R33次/分，BP 110/80mmHg。重症病容，口唇发紫，半卧位，嗜睡；颈静脉怒张，心界向两侧扩大，心尖区可听到明显收缩期杂音，肺动脉瓣第二音亢进。两肺可闻广泛湿性罗音.腹膨隆，可闻移动性浊音。肝于肋下6cm，压痛；脾于肋下3 cm。指端呈杵状，下肢明显凹陷性水肿。 。病例第60页，共128页。实验室检查：红细胞3.01012/L白细胞18109/L中性粒细胞占90%尿量300-500ml/日 少量蛋白和红细胞尿胆红素（+）血浆总胆红素31.6mol/L（正常17.1）直接胆红素12.8mol/L (正常50%第64页，共128页。压力指标： LVEDP

31、 正常值 0.67 1.60Kpa （5 12mmHg） LAP 正常值 0.27 1.60Kpa （2 12mmHg） PAP 正常值 1.60 3.340.541.73KPa （12 25413mmHg） 平均压 10.67 25.3KPa（8 19mmHg）PCWP 正常值 0.67 1.60KPa（5 12mmHg） 13 20mmHg（轻度增高） 2130mmHg（中度增高） 30mmHg（重度增高） 通常 PCWP18mmHg（2.4KPa）肺底出现湿罗音 PCWP25mmHg（3.3KPa）湿罗音12肺野 PCWP30mmHg（4KPa）肺水肿 若无二尖瓣狭窄时，PCWP=LAP

32、=LVEDP 第65页，共128页。Treatment of chronic heart failure Principle: alleviate symptoms ,improve life quality.treatment for primary disease and precipitating causesAntagonism of neurohumoral activationinhibition of progressive ventricular remodelingreduce mortality and extend life.第66页，共128页。Treatment of

33、 chronic heart failureGeneralPharmacologic treatmentNon-medicine treatment第67页，共128页。General treatment1.一般患者应采取高枕位睡眠；较重者采取半卧位或坐位。2.限制体力活动，心力衰竭较重的患者以卧床休息为主；心功能改善后，应适当下床活动，以免下肢血栓形成和肺部感染。3.一定要戒烟、戒酒，保持心态平衡，同时还要保证充足的睡眠。4.少量多餐，低盐饮食,每日食盐不宜超过5克。5.按医嘱服药；预防呼吸道感染；育龄妇女要做好避孕。第68页，共128页。General treatmentdecreased

34、 burdensincreased systole powerAnti-neurohumoral activation第69页，共128页。General treatmentdecreased burdensincreased systole powerAnti-neurohumoral activation1.Lifestyle managementEducationRegulate weightDietary management:salt take2.Rest and action3. Treatment for primary disease and precipitating 第70

35、页，共128页。General treatmentdecreased burdensincreased systole powerAnti-neurohumoral activation1.Rest2. Dietary management:salt take3. Diuretics furosemidedihydrochlorothiazide ( potassium-losing) antistone (potassium-sparing)第71页，共128页。The main point of diuretics application对于有症状的心衰，当液体负荷过重已表现为肺淤血或外周

36、水肿时，利尿剂是基本的治疗。应用利尿剂可迅速改善呼吸困难并增加运动耐量（I类建议，证据级别A）尚无大型随机对照试验评估这类药物对症状和生存的影响。如能耐受，利尿剂始终应与ACEI和-受体阻滞剂一起使用。（I类建议，证据级别C）。第72页，共128页。 襻利尿剂应作为首选。噻嗪类仅适用于轻度液体潴留、伴高血压和肾功能正常的心衰患者(I类，B级)。利尿剂通常从小剂量开始(氢氯噻嗪25 mg/d，呋塞米20 mg/d，托塞米10 mg/d),逐渐加量。一旦病情控制即以最小有效量长期维持。每日体重变化是最可靠检测利尿剂效果和调整利尿剂剂量的指标。长期服用利尿剂应严密观察不良反应的出现如电解质紊乱、症状

37、性低血压，以及肾功能不全，特别在服用剂量大和联合用药时（类，B级）。The main point of diuretics application第73页，共128页。General treatmentdecreased burdensincreased systole powerAnti-neurohumoral activation1.Rest2. Dietary management:salt take3. Diuretics4. Vasodilator sodium nitroprusside(SNP) Nitroglcerin（硝酸甘油）regitine(酚妥拉明)第74页，共128

38、页。The main point of Vasodilator application直接血管扩张剂对于CHF的治疗无特殊作用。（类，A级）血管扩张剂可用于不能耐受ACEI或ARBs的患者；伴有心绞痛或高血压可考虑应用（类，B级）禁忌证： 血容量不足，低血压、肾功能衰竭 心脏流出道或瓣膜狭窄患者第75页，共128页。General treatmentdecreased burdensincreased systole powerAnti-neurohumoral activation1.Digitalis （1）effection:Positive inotropic： inhibit Na+

39、-K+-ATP enzyme introcellular Na+、K+ Na+-Ca2+exchange introcellular Ca2+ myocardial systole power introcellular K+ ，digitalis poisoning第76页，共128页。第77页，共128页。General treatmentdecreased burdensincreased systole powerAnti-neurohumoral activation1.Digitalis （1）effection:Positive inotropic：Electrophysiolo

40、gical Inhibit condution system, espicially atriventricular junction. Improve the autorhythmicty of atrium, junction region and ventricle.第78页，共128页。General treatmentdecreased burdensincreased systole powerAnti-neurohumoral activation1.Digitalis （1）effection:Positive inotropic：ElectrophysiologicalPar

41、asympathetic stimulating anti-sympathetic nerve exciting 第79页，共128页。General treatmentdecreased burdensincreased systole powerAnti-neurohumoral activation1.Digitalis （1）effection:Positive inotropic：ElectrophysiologicalParasympathetic stimulatingRole in the renal tubule cells reducing sodium reabsorpt

42、ion inhibit the secretion of renin 第80页，共128页。General treatmentdecreased burdensincreased systole powerAnti-neurohumoral activation1.Digitalis （2）application indication: chronic congestive heart failure complicated by atrail flutter and fibrillation and a rapid ventricular rate第81页，共128页。General tre

43、atmentdecreased burdensincreased systole powerAnti-neurohumoral activation1.Digitalis （2）application contraindication（禁忌症）:WPW with AF degree AVB , degree AVBsick sinus syndrome(SSS)Hypertrophic cardiomyopathy (HOCM)severe mitral stenosis(SMS)acute myocardiac infarction(first 24 h第82页，共128页。General

44、treatmentdecreased burdensincreased systole powerAnti-neurohumoral activation1.Digitalis (3) digitalis poisoningfactors： K+ ,O2 ,Clincal expression: gastric bowel reaction; arrhythmia; neurological and visual changeDiagnosis： 2.0 ng/ml第83页，共128页。Arrhythmia of digitalis poisoningVentricular Premature

45、 beatNonparoxysmal atrioventricular junctional tachycardia非阵发性房室交界性心动过速Atrial Premature beatAtrial fibrillaton Atrioventricular block ST-T change like fishhookCharacteristic feature第84页，共128页。第85页，共128页。General treatmentdecreased burdensincreased systole powerAnti-neurohumoral activation1.Digitalis

46、Treatment of digitalis poisoningdrug withdrawaltachycadia:supply K+ , Lidocain ivbradicadia： atropin iv, not suitable for pacemaker not suitable for isoprenaline disable cardioerter第86页，共128页。General treatmentdecreased burdensincreased systole powerAnti-neurohumoral activation 1、 Digitalis2、-excitan

47、tDopamine： NE precursor2g/kg.min Dopamine -R(+) expand renal artery2-5 g/kg.min 1 2-R(+) myocardial contractility, Vasodilate5-10 g/kg.min -R(+) BP ,HR Dobutamine： Dopamine derivatives 2g/kg.min 10g/kg.min Vasodilate, HR -small effects第87页，共128页。General treatmentdecreased burdensincreased systole po

48、werAnti-neurohumoral activation 1、 Digitalis2、-excitant3、Phosphodiesterase inhibitors 1、effect: restrain activity of phosphodiesterase ， the degradation of cAMP(-) cAMP Ca2+ channel activation Ca2+ -inflowmyocardial contractility 第88页，共128页。General treatmentdecreased burdensincreased systole powerAn

49、ti-neurohumoral activation 1、 Digitalis2、-excitant3、Phosphodiesterase inhibitors 1、effect:2、indications ：refractory heart failureend-stage heart failure before heart transplantation 第89页，共128页。General treatmentdecreased burdensincreased systole powerAnti-neurohumoral activation 1、 Digitalis2、-excita

50、nt3、Phosphodiesterase inhibitors 1、effect:2、indications ：3、drugs： 氨力农(Amrinone) VD 5-10 g/kg.min 米力农(Milrinone) VD 0.5 g/kg.min第90页，共128页。General treatmentdecreased burdensincreased systole powerAnti-neurohumoral activation 1、 Digitalis2、-excitant3、Phosphodiesterase inhibitors 1、effect:2、indications

51、 ：3、drugs： 4、defect ： side-effect ; mortality 第91页，共128页。 AII 产生是通过多种通道 血管紧张素原肾素血管紧张素 I(1-10) Ang II（1-8）ACEAT1AT2血管收缩 增殖醛固酮增加血管扩张 抗增殖Ang1-7Ang1-7受体激活血管扩张 抗增殖ARB第92页，共128页。General treatmentdecreased burdensincreased systole powerAnti-neurohumoral activation 1、 RAAS inhibitorAngiotensin Converting En

52、zyme Inhibitors(ACEI) dilate blood vessels inhibit RAS, sympathetic system reverse the ventricular remodeling improve blood flow dynamics Improve endothelial function AT ,Inhibit the degradation of bradykinin第93页，共128页。General treatmentdecreased burdensincreased systole powerAnti-neurohumoral activa

53、tion 1、 RAAS inhibitorAngiotensin Converting Enzyme Inhibitors(ACEI) Clinical status symptoms , exercise tolerance mortality delay the progress of heart failure reducing hospitalization rates prevent HF after myocardial infarction 第94页，共128页。General treatmentdecreased burdensincreased systole powerA

54、nti-neurohumoral activation 1、 RAAS inhibitorAngiotensin Converting Enzyme Inhibitors(ACEI) Captopril 6.2525mg 23/d Enalapril 10 mg 2/d Benazepril 510 mg/d Perindopril 24 mg/d Fosinopril 510 mg/d Ramipril 5 mg/d第95页，共128页。General treatmentdecreased burdensincreased systole powerAnti-neurohumoral act

55、ivation 1、 RAAS inhibitorAngiotensin Converting Enzyme Inhibitors(ACEI) application methods starting with small dosesif tolerated , gradually increase the dosemonitoring of renal function and ions renal function change, high potassium, dry cough, angioedema 第96页，共128页。General treatmentdecreased burd

56、ensincreased systole powerAnti-neurohumoral activation 1、 RAAS inhibitorAngiotensin Converting Enzyme Inhibitors(ACEI) Contraindication: anuric renal failure pregnancy and brest feeding woman allergeRelative Contraindication: renal artery stenosis bilaterally Cr225 mol/l k+5.5mmol/l hypotension第97页，

57、共128页。General treatmentdecreased burdensincreased systole powerAnti-neurohumoral activation 1、 RAAS inhibitorAngiotensin Converting Enzyme Inhibitors(ACEI) Angiotensin II receptor antagonist (ARB) AT-AT1 receptor Inhibit RAS No affecting the degradation of bradykinin第98页，共128页。General treatmentdecre

58、ased burdensincreased systole powerAnti-neurohumoral activation 1、 RAAS inhibitorAngiotensin Converting Enzyme Inhibitors(ACEI) Angiotensin II receptor antagonist (ARB)application methods less dry cough and angioedema when HF , first chose ACEIwhen HF , should not be combined application of ACEI and

59、 ARB Losartan 50mg/d;valsartan 80mg/d第99页，共128页。General treatmentdecreased burdensincreased systole powerAnti-neurohumoral activation 1、 RAAS inhibitorAngiotensin Converting Enzyme Inhibitors(ACEI) Angiotensin II receptor antagonist (ARB)Aldosteroneantagonists spironolactone(SPI)螺内酯potassium-sparing

60、 diuretic reverse the ventricular remodeling improve prognosis第100页，共128页。General treatmentdecreased burdensincreased systole powerAnti-neurohumoral activation 1、 RAAS inhibitorAngiotensin Converting Enzyme Inhibitors(ACEI) Angiotensin II receptor antagonist (ARB)Aldosteroneantagonists renin inhibit